Human Anti-Glycosphingolipids Antibodies in Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is classified as a combination of several disorders and is characterized by an immune-mediated attack on the peripheral nervous system (PNS), particularly on the myelin sheath and axon of sensory and motor nerves, resulting in demyelination and/or axonal degeneration. Many of the previous clinical studies have suggested that GBS is most likely triggered by the appearance of enteritis and neuritis induced by microbial pathogens such as Campylobacter jejuni (. C. jejuni). There is evidence that interspecies transmission of C. jejuni-induced GBS can be transmitted from chickens to humans, but this possibility has not been epidemiologically demonstrated. The preceding infectious event is associated with increased antibody titers of glycosphingolipids (GSLs), especially certain acidic GSLs such as gangliosides and sulfoglycolipids, in patients with GBS. These anti-acidic GSL antibodies frequently express cross-reactivity between cell surface carbohydrate antigens of the infecting microbes and host cells. This cross-reactivity likely arises as the result of molecular mimicry between the carbohydrate epitopes and the GSLs of the PNS and bacterial (e.g., C. jejuni) lipo-oligosaccharides (LOS). Anti-ganglioside antibodies have been shown to involve about 60% of patients with GBS. Recently the presence of reacting antibodies with a mixed form of gangliosides (e.g., GD1a and GD1b) has been demonstrated. These antibodies have been overlooked and concealed in certain patients' sera that are "anti-ganglioside antibody negative." This unusual class of autoantibodies has been termed anti-ganglioside-complex (GSC) antibodies and is also implied in the pathogenesis of GBS and some of its variants. Pathogenically, these GBS-related antibodies have been shown to induce nerve injury, including demyelination and axonal degeneration, leading to serious loss of conduction velocity or conduction block. Recent studies also revealed that interruption of neurotransmission could occur as a result of interaction of anti-ganglioside antibodies with ion channels at the nodes of Ranvier. Accumulating ex  vivo electrophysiologic evidence suggests that ganglioside molecular mimicry may be responsible for muscle weakness, possibly via interference with ion channels as well as neuromuscular junctions.